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Mall developer has big plansDecember 06,2013Mall developer
has big plans
BURLINGTON The prospective owner of a mall in downtown Burlington has some big plans to bring some big-name retailers to town.
Devonwood Investors of New York City is set to close on the Burlington Town Center mall next week.
The Burlington Free Press reported that Devonwood plans to add a new anchor tenant, such as L.L. Bean, to draw more shoppers to the area.
Formerly confidential records obtained by the newspaper also make mention of expanding the mall to accommodate a big-box store and names Target as an example.
In its memo filed with the city, Devonwood also says it is contemplating a hotel with meeting and conference facilities.
The closing is scheduled for Dec. 16.
The Associated PressMORE IN Vermont NewsCOLCHESTER Industrial hemp growers have harvested their second crop since the Vermont... Full StoryMIDDLEBURY A western Vermont woman is dead after the pickup truck she was riding in crashed... Full StoryWASHINGTON Vermonts congressional delegation is divided between outright opposition and wait... Full Story
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A candidate for one of the most backward wines of the vintage, and still needing probably 8-10 more years of cellaring, the Brunel family tends to make this cuvee to age as well as a top Bordeaux. It is one of the exceptions to the rule in Chateauneuf du Pape. The 1998 has a dark plum/ruby/purple color, with notes of graphite, chocolate, espresso roast, black berry, and cassis. Aromatically, one doesn't see much Chateauneuf du Pape character, but the oak has been totally absorbed, the wine is full-bodied, and I suspect more and more typicity will evolve as it hits its adolescent state. Forget it for another 3-5 years, as this is a wine capable of lasting 30+ years.
This is ultra everything--ultrablack, ultrathick, ultrasmooth, ultrabig--but it works. With tar, petrol and superextracted black fruit, it tastes velvety and balanced, not at all heavy or new oakish.
The item you have chosen is not in stock in our retail stores or within our main warehouse.
1998 Lucien et Andre Brunel "Les Cailloux" Châteauneuf-du-Pape
1998 Château de Beaucastel Châteauneuf-du-Pape
2005 Château de Montfaucon "Baron Louis" Côtes du Rhône
1998 Château La Nerthe "Cuvée des Cadettes" Châteauneuf-du-Pape
2005 Tardieu Laurent "Cuvée Speciale" Châteauneuf-du-Pape

subset: commoncrawl


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On sale
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Report NEP-NET-2009-07-03This is the archive for NEP-NET, a report on new working papers in the area of Network Economics. Yi-Nung Yang issued this report. It is usually issued weekly.
Subscribe to this report: email, RSS or Twitter.
Other reports in NEP-NET
The following items were announced in this report:
- Joel BAUM & Robin COWAN & Nicolas JONARD, 2009. "Network-independent partner selection and the evolution of innovation networks," Working Papers of BETA 2009-23, Bureau d'Economie Théorique et Appliquée, UDS, Strasbourg.
- Bojanowski, Michał & Corten, Rense & Westborck, Bastian, 2009. "The structure and dynamics of the global network of inter-firm R&D partnerships 1989-2002," MPRA Paper 15741, University Library of Munich, Germany.
- Jörg Franke & Tahir Öztürk, 2009. "Conflict Networks," Ruhr Economic Papers 0116, Rheinisch-Westfälisches Institut für Wirtschaftsforschung, Ruhr-Universität Bochum, Universität Dortmund, Universität Duisburg-Essen.
- Vereecke, A. & De Meyer, A., 2009. "The dynamic management of manufacturing networks," Vlerick Leuven Gent Management School Working Paper Series 2009-15, Vlerick Leuven Gent Management School.
- Moritz Müller & Robin COWAN & Geert Duysters & Nicolas JONARD, 2009. "Knowledge Structures," Working Papers of BETA 2009-24, Bureau d'Economie Théorique et Appliquée, UDS, Strasbourg.
- Francesco De Sinopoli & Carlos Pimienta, 2009. "Costly Network Formation and Regular Equilibria," Discussion Papers 2009-05, School of Economics, The University of New South Wales.
- Item repec:dgr:uvatin:20090048 is not listed on IDEAS anymore


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Converging evidence suggests a central role for dysfunction of the subgenual anterior cingulate cortex (sgACC) in the pathophysiology of major depressive disorder (MDD). Underlying mechanisms may include altered GABAergic function. Expression of somatostatin (SST), an inhibitory neuropeptide localized to a subset of GABA neurons, has been shown to be lower in the dorsolateral prefrontal cortex of male MDD subjects. Here, to investigate whether alterations in SST may contribute to sgACC dysfunction in MDD, and whether the alterations display sex-specificity, we measured sgACC SST at the mRNA and precursor peptide levels in a large cohort of subjects with MDD. SST mRNA levels were analyzed by quantitative PCR (qPCR) in the postmortem sgACC from male (n=26) and female (n=25) subjects with MDD and sex-matched subjects with no psychiatric diagnosis (n=51). Prepro-SST protein levels were assessed in a subset of subjects (n=42 pairs) by semi-quantitative western blot. The mRNA expression of SST was significantly reduced by 38% in female subjects and by 27% in male subjects with MDD. The characteristic age-related decline in SST expression was observed in control (Pearson R=−0.357, p=0.005) but not MDD (R=−0.104, p=0.234) subjects, as low expression was detected across ages in MDD subjects. Protein expression was similarly reduced by 19% in both MDD groups, and findings were more robust in female (p=0.0056) than in males (p=0.0373) compared to respective controls. In conclusion, low SST represents a robust pathological finding in MDD. Specifically, alterations in SST signaling and/or SST-bearing GABA neurons may represent a critical pathophysiological entity that contributes to sgACC dysfunction and that matches the high female vulnerability to develop MDD.
An extended corticolimbic circuitry regulating mood has been implicated in the pathophysiology and treatment of MDD (Seminowicz et al., 2004). One of the components of this circuitry, the sgACC has been shown to play a major role in both the induction of the depressive state and in treatment response to multiple modalities (Agid et al., 2007). For example, positive response from a baseline depressed state, regardless of treatment modality (electroconvulsive therapy, deep brain stimulation, antidepressants or placebo) is associated with a decrease in sgACC activity (George et al., 1999; Mayberg et al., 1999; Nobler et al., 2001; Mayberg, 2002). Furthermore, with tryptophan depletion or recollection of a sad memory, transient increase in sgACC activity occurs in healthy non-depressed subjects (Mayberg et al., 1999; Talbot and Cooper, 2006).
Increasing evidence suggests an impaired excitation/inhibition balance in MDD potentially mediated by decreased GABA content, as observed by proton magnetic spectroscopy in occipital and frontal cortices (Sanacora et al., 1999; Sanacora et al., 2004), or by transcranial magnetic stimulation paradigms (Levinson et al., 2010), which is reversed after antidepressant treatments (Sanacora et al., 2002; Sanacora et al., 2003). As GABA synthesis and release is found largely in inhibitory neurons, these results suggest that altered GABA neuronal microcircuitry and associated inhibition may contribute to altered sgACC function in MDD (Valentine and Sanacora, 2009). Dysregulation of the neuronal/interneuronal microcircuitry within the sgACC has yet to be elucidated. Morphometric studies have reported reduced density and size of cortical neurons (Brodmann transitional area 10-47, 47) (Rajkowska et al., 1999), recently attributed to interneurons in some studies (Brodmann area 9, 17, and 47), but not all (Brodmann Area 24) (Rajkowska et al., 2007; Maciag et al., 2010). The nature of the affected cells in MDD is beginning to be characterized, using cellular markers expressed in distinct interneuronal populations. Accordingly, the density of calbindin-immunoreactive (CB) interneurons was significantly reduced in occipital and orbitofrontal cortices of MDD subjects (Rajkowska et al., 2007; Maciag et al., 2010), but unchanged in two other studies in cingulate and dorsolateral prefrontal cortex (Beasley et al., 2002; Cotter et al., 2002). In the context of a survey of markers for GABA neuron populations, we recently identified a significant decrease in SST expression in the dorsolateral prefrontal cortex of subjects with MDD (Sibille et al., 2010). SST's original function was identified as inhibition of human growth hormone, but further studies have shown a generally inhibitory function across different organ systems, including the central nervous systems (CNS) (Viollet et al., 2008). SST acts presynaptically by inhibiting glutamate release, activating potassium leak current, or inhibiting voltage-dependent calcium currents, depending on the anatomical structure (Baraban and Tallent, 2004). Postsynaptically, SST inhibits neurons through dendritic hyperpolarization, by activation of either voltage dependent (IM) or voltage-independent (IK(L) ) K+ currents and inhibition of voltage-activated Ca2+ currents and consecutive Ca2+-induced currents (Baraban and Tallent, 2004). Furthermore, SST is upregulated in the hippocampus of a rat model of electroconvulsive treatment (Newton et al., 2003). As a neuropeptide in the CNS, SST is co-localized and co-released in a GABA+/CB+ interneuron subset (Viollet et al., 2008).
In this study, we first sought to determine SST expression in MDD subjects compared to subjects with no psychiatric diagnosis in the sgACC, hence extending our prior studies in the dorsolateral prefrontal cortex. Based on prior evidence suggesting sex differences in disease-related SST changes (Mellios et al., 2008), and in view of the robust sexual dimorphism in MDD prevalence (Kessler et al., 2003), we also determined whether MDD-related SST expression changes display sex-specific patterns, by comparing MDD-related SST changes between two large cohorts of male and female MDD subjects and subjects with no psychiatric diagnosis. Moreover, since age-associated decrease in SST mRNA can explain within-group variability in measures (Sibille et al., 2010), we further investigated the effect of age in the control and MDD subgroups. Finally, as the short half-life of the SST protein complicates its quantification in postmortem tissue (Hayes et al., 1991), using quantitative Western blot techniques, we measured SST prepro-peptide, as the closest protein match, to indirectly estimate SST protein levels in MDD.
After consent was obtained from the next of kin, brain specimens in the Brain Tissue Donation Program at the University of Pittsburgh were obtained during autopsies conducted at the Allegheny County Medical Examiner's Office (Pittsburgh, PA, USA). Two cohorts of MDD subjects were examined (male, n=26; female, n=25). Each subject was matched for sex and as closely as possible for age with one control subject (Tables (Tables11--2).2). Subject groups did not differ in mean age, PMI, RNA integrity number (RIN), RNA ratio, or brain pH as determined by one way ANOVA (p>0.05).
For all subjects, consensus DSM-IV diagnoses of MDD were made by an independent committee of experienced clinical research scientists at a case conference utilizing information obtained from clinical records, toxicology exam and a standardized psychological autopsy (Glantz et al., 2000). This latter incorporates a structured interview, conducted by a licensed clinical psychologist with family members of the index subject, to assess diagnosis, psychopathology, medical, social and family histories, as well as history of substance abuse using the structured clinical interview for DSM disorders (SCID) and other assessment tools (Spitzer et al., 1992). Using the information judged to be reliable at the diagnostic conference, a symptom score (1= unequivocal yes; 0.5= unsure or subthreshold; 0= unequivocal no) was calculated based on the presence at time of death, or a prior history, of nine symptoms of depression: depressed mood, anhedonia, appetite disturbance, sleep disturbance, psychomotor change, anergia, self-recrimination, impaired concentration of decision-making, and suicidality. All procedures were approved by the University of Pittsburgh's Committee for the Oversight of Research Involving the Dead and Institutional Review Board for Biomedical Research.
As previously described (Volk et al., 2000), the right hemisphere of each brain was sectioned along the coronal plane, immediately frozen and stored at −80°C. Samples containing all six cortical layers, but excluding the adjacent white matter, were harvested from coronal cryostat sections (20 μm) at the anatomical level corresponding to sgACC (Brodman area 25) and collected into tubes containing Trizol reagent (Invitrogen, Carlsbad, CA, USA) for RNA isolation. The location of the sgACC was determined from Nissl-stained sections using cytoarchitectonic criteria as previously described (Volk et al., 2000). Total RNA was isolated from Trizol homogenates of sections, further purified by RNeasy columns (Qiagen, Valencia, CA, USA) and RNA integrity (RIN) was assessed by measuring using the Bioanalyzer 2100 (Agilent Technologies, Walbronn, Germany) (Imbeaud et al., 2005). To generate cDNA, 1μg total RNA was mixed with oligo-dT promers and SuperScript II Reverse Transcriptase (RT) as per manufacturer's protocol (Invitrogen Carlsbad, CA).
qPCR analyses (Glorioso et al., 2006) were performed using SST-specific primers and three internal controls on sgACC cDNA samples as described previously (Sibille et al., 2009). In brief, small PCR products (80–120 base-pairs) were amplified in quadruplets on an Opticon real-time PCR machine (BioRad Cie, Waltham, MA, USA), using universal PCR conditions (65C–59C touch-down, followed by 35 cycles (15s at 95C, 10s at 59C and 10s at 72C). cDNA (150pg) was amplified in 20μl reactions (0.3× Sybr-green, 3mM MgCl2, 200μm dNTPs, 200μm primers, 0.5 unit Platinum Taq DNA polymerase (Invitrogen, Carlsbad, CA, USA)). Primer dimers were assessed by amplifying primers without cDNA and retained if they produced no dimers or non-specific signal only after 35 cycles. Each qPCR run included two subjects per pair, 3 pairs with amplification of all 4 transcripts of interest in quadruplicate using a plate with 96 wells (6 subjects × 4 transcripts × 4 replications). Three internal control transcripts encoding for beta-actin, cyclophilin A, and glyceraldehyde-3-phosphate dehydrogenase were amplified for each subject. The difference in cycle threshold for SST was calculated by subtracting the mean cycle threshold for the three internal controls from the cycle threshold of the SST transcript. This difference in cycle threshold (dCt) represents the log2-transformed expression ratio of SST to the geometric mean of the three internal control transcripts (Vandesompele et al., 2002); and the relative expression level of SST was determined as 2−ddCt*10.
Diagnosis-related expression differences in SST signal was determined by analysis of covariance (ANCOVA) using SPSS (SPSS, Inc., Chicago, IL). The qPCR data were averaged across the four replicates and transformed into relative expression levels (2−ddCt*10) so that plots of data are intuitive (i.e. higher values represent greater relative expression). To determine relevant covariates, nominal factors were each tested as the main factor in single ANOVA, and scale covariates were tested by Pearson correlation. Multiple comparisons with covariates (see result section for specific covariates used in each ANCOVA) were controlled by adjusting for simultaneous inference of significance levels using the Bonferroni-Holm method (Volk et al., 2000) in which p-values are ordered from the smallest (i=1) to the largest (i=N) among multiple comparisons; the significance level for each comparison is defined as α=0.05/([N+1]-i). MDD/control pairing and covariate factors with significant effects were used in the ANCOVA model with SST mRNA as the dependent variable and subject group as the main effect. Exploratory analysis including multiple covariate factors with trend-like effects (p<0.2) in the ANCOVA model did not affect the results and are not reported. Variance homogeneity was tested by the Kruskal-Wallis test.
Acetone precipitation of proteins was carried out following the RNA extraction from the TRIzol samples of brain tissues. The lower red phenol-chloroform phase was used for protein isolation, using ethanol to precipitate DNA, and acetone to extract protein from the supernatant. Following extensive washes, the dried pellet was dissolved in 1x SDS buffer. The supernatant was collected after 5 minute centrifugation at 14,000 rpm. An aliquot was used for protein quantification using PIERCE BCA assay (PIERCE, Rockford, IL). Confirmation of expected sizes for pre-pro SST (14kD) and beta actin (37kD) were performed with a HEPES-based buffer system. We also previously confirmed the specificity of this antibody by the absence of immunoreactivity in SST knockout mice (Sibille et al., 2010). For comparative quantification, 5μg of protein samples were determined to be in the linear range of Western quantification and were used here. Samples were resolved by SDS PAGE in 10% Tris/glycine gels and transferred to PVDF membrane.
Western blot analysis was performed following SDS-PAGE using the Odyssey system (LI-COR Biosciences, Lincoln, NE) as described (Sibille et al., 2009). In brief, gel-transferred PVDF membrane were blocked in LI-COR blocking buffer and incubated with mouse anti-actin, at 0.5ug/mL (Sigma #A 2228) and rabbit polyclonal primary antibody for prepro-somatostatin (prepro-SST) at 0.5ug/mL (ab53165, Abcam, Cambridge, MA). Fluorescent IR Dye 680 anti-Rabbit and fluorescent IR Dye 800 anti-mouse (LI-COR Biosciences) secondary antibodies were used in signal detection. The Li-Cor Odyssey Infrared imaging system captures the whole dynamic range of infrared fluorescence using small quantities of protein (5ug per lane used here). Dual signals were detected and prepro-SST/Actin signal ratios were calculated. Samples were processed in matched pairs on the same gel and results were replicated for a total of three different western blots. To control for gel-to-gel variability, two parallel statistical approaches were applied. First, paired t-tests were run in age- and sex-matched pairs, and group results were combined across the three runs using the Stouffer's approach, which considers p-values, sample sizes, and effect directions (Whitlock, 2005). Second, an ANCOVA model with age, pair, PMI and batch processing as covariate factors was applied and group results were similarly combined across the three runs using the Stouffer's approach. Significance was set at α=0.05.
For scale cofactors (age, pH, RNA ratio, RIN, PMI), only age significantly correlated with SST expression (Pearson R=−0.232; p=0.01). No nominal cofactors (sex, race, depressed state, antidepressants, comorbid substance abuse, suicide, cohort), were statistically significant after Bonferroni-Holm correction. SST mRNA relative expression and signal, as well as protein ratios were normally distributed, alone and with sex and age as covariates. As we investigated putative sex differences, age and sex were included into an ANCOVA model. We observed a significant reduction of 33% in SST mRNA expression in the combined male/female MDD subject group compared with control subjects (F1,98=4.540, p=0.036) (Figure 1A).
As the incidence of depression in women is approximately twice that of men (Kessler et al., 2003), we explored the potential contribution of sex to differential SST expression in MDD by separately assessing SST changes in male and females. For scale cofactors (age, pH, RNA ratio, RIN, PMI) in the male group (n=26 pairs), only age was significant (Pearson R=−0.346, p=0.006). None of the nominal cofactors (sex, race, depressed state, antidepressants, comorbid substance abuse, suicide, cohort) were statistically significant. Including age in the ANCOVA model, subject group was statistically significant and sgACC SST transcript expression was reduced by 27% in male MDD subjects compared to controls (F2,48=4.295, p=0.044) (Figure 1B). In the female group (n=25 pairs), none of scale (including age) or nominal cofactors were significant by one-way ANOVA or Pearson correlation. sgACC SST transcript expression was significantly reduced by 38% in female MDD subjects compared to controls (F1,48=7.771, p=0.008) by ANOVA (Figure 1C). Hence, SST mRNA expression was significantly reduced in MDD subjects, and to a larger extent and greater statistical significance in female MDD subjects.
To investigate whether SST levels related to disease severity, we assessed correlations between SST qPCR levels and depressive symptoms, as determined by psychological autopsy (See Methods). We observed a moderate negative correlation between past depressive symptom score and SST expression (R=−0.276, p=0.025). When segregated by sex, the effect was more profound in female MDD subjects (R=−0.528, p=0.003) and absent in male MDD subjects (R=0.023, p=0.456). There was no correlation with symptom number at time of death and SST expression for the combined or sex-specific group (all R < 0.114; all p > 0.215).
The expression of SST is significantly downregulated with age (Hoffman and Sladek, 1980; Hayashi et al., 1997; Erraji-Benchekroun et al., 2005), which we showed can explain some of the experimental variability that is observed in SST measures (Figure 1; see also (Sibille et al., 2010)). As described, age was a significant covariate by ANCOVA for all samples and in the male cohort. When subjects were subdivided into control and MDD groups, the age-SST correlation remained significant in controls (Pearson R=−0.357, p=0.005), but not in the MDD group (R=−0.104, p=0.234), as SST mRNA levels were lower at all ages in most subjects with MDD (75% cases) compared to age-matched controls (Figure 2A). Similarly, when segregated by sex, male control subjects displayed a statistically significant inverse correlation with age (R=−0.509, p=0.004), but not MDD subjects (R=−0.143, p=0.243) (Figure 2B). In female subjects, decreased SST with increasing age was at the trend levels in controls (R=−0.278, p=0.089) and not significant in MDD subjects (R=−0.116, p=0.291).
To assess whether decreased mRNA translated to decreased protein level, we investigated tissue content level of the prepro-peptide for SST. SST's active form has been shown to rapidly degrade within the first few hours postmortem, which complicates its analysis in postmortem cohort (Hayes et al., 1991). However, we have now shown that the precursor protein is present in the postmortem tissue (Sibille et al., 2010). The prepro-SST immunoreactive band (Figure 3A) migrated at the expected size and was not correlated with PMI (R=−0.37, p=0.38). Using western blot analysis, the SST prepro-peptide was decreased by 19% in MDD subjects compared to control subjects (n=42 pairs available, males, n=26; females, n=16; 3 replicate experiments; Stouffer's z-score test on paired T-test, p=0.0001; Stouffer's z-score test on ANCOVA results, p=0.0005) (Figure 3A). There was no statistically significant correlation between prepro-SST protein levels and age in control or depressed subjects, however this negative result may have been complicated by the increased variability in measures obtained across multiple gels (coefficient of variation (CV) across blots: CV=0.47; and within blots: CV=0.29). After segregation by sex, the reduction remained at 19% in male MDD subjects (3 replicates, Stouffer's z-score on paired T-test, p=0.002, and on ANCOVA results, p=0.0373) (figure 3A). In female MDD subjects, SST prepro-peptide was similarly decreased by 19%, but at higher statistical significance (3 replicates, Stouffer's z-score on paired T-test, p=0.0001; Stouffer's z-score test on ANCOVA results, p=0.0056).
We observed a weak correlation or no correlation (0.04<p-value<0.46) between pre-proSST protein and mRNA levels in the combined or sex-specific groups, which may reflect the blot to blot variability in the assessment of protein levels, and/or additional processing regulation of the precursor protein into functional SST.
Results from this study show that SST is downregulated by ~30% at the RNA level and by ~20% at the precursor protein level in the sgACC of male and female subjects with MDD compared to normal non-psychiatric control subjects. These results extend our prior findings of reduced SST mRNA expression from the dorsolateral prefrontal cortex (Sibille et al., 2010) to the subgenual ACC, a central brain area in a corticolimbic circuitry of mood regulation, hence representing a robust and replicated molecular phenotype for major depression. Comparable results were obtained in male and female subjects with MDD, suggesting a similar pathological entity across sex groups, but the extent and/or statistical significance of the findings were more robust in female subjects (or alternatively more variable in males), both at the mRNA and protein levels. Results were independent of cofactors associated with clinical features of the illness or technical parameters of brain collection, with the exception of age and symptom number. Similar to our prior observation in the dorsolateral prefrontal cortex, we show that the characteristic downregulation of SST mRNA with age was blunted in MDD subjects, as SST was low at most ages in those subjects. Notably, the age effect was attenuated in both control and MDD female subjects, potentially explaining the less variable findings in this cohort, due to a decreased analytical confounding effect of age in that group. Together, these results establish low SST as a frequently observed pathological finding that is shared between the dorsolateral prefrontal cortex and the sgACC, and that corresponds with the elevated vulnerability and prevalence of MDD in female subjects. The findings were present regardless of the depressive syndrome was fully present or in full/partial remission at time of death, moderately and inversely correlated with symptom numbers, together suggesting that low SST may represent a critical vulnerability factor to develop MDD, and that additional factors may further determine the severity of the illness.
In this report, we also demonstrated a reduction in the level of the prepro-SST peptide. Since direct levels of SST are difficult to measure in postmortem tissue due to rapid postmortem peptide processing (Hayes et al., 1991), we speculate that low prepro-SST may represent an adequate proxy of SST level, although additional regulatory steps and effects of MDD on peptide processing likely occurred, as suggested by the lack of subject-wise correlation with RNA levels. The extent of the reduction of relative prepro-SST protein expression was the same for both male and female depressed subjects, but the statistical significance was more robust in female subjects.
There is a historical literature associating low SST levels in cerebrospinal fluid (CSF) with depressed states (Post et al., 1988; Rubinow et al., 1988). SST was an early target of investigation for depression as the major neuropeptide that inhibits the hypothalamic-pituitary-adrenal (HPA) axis, inhibiting corticotrophin releasing hormone (CRH) and the stress response (Post et al., 1988). SST expression was also shown to be positively regulated by brain-derived neurotrophic factor (BDNF) and to inversely correlate with age (Hoffman and Sladek, 1980; Hayashi et al., 1997; Erraji-Benchekroun et al., 2005). The etiological factors leading to reduced SST are not known and may include decreased BDNF-mediated transcriptional activation, through decreased TrkB and/or TrkC receptors availability or signaling (Rage et al., 1999; Jin et al., 2003; Hashimoto et al., 2005; Glorioso et al., 2006) and/or through changes in methylation status at the SST promoter. In major unipolar depression or bipolar depression, SST was shown to be transiently decreased in CSF and normalized with recovery (Post et al., 1988; Pantazopoulos et al., 2007). In contrast other disorders, such as Alzheimer's disease, showed an irreversible decrease in SST concentrations in the CSF (Post et al., 1988). Elevated CSF SST levels have also been reported in mania compared to subjects with MDD, schizoaffective disorder, or schizophrenia (Sharma et al., 1995). SST was also investigated in the context of its influence on sleep quality, as a potential therapeutic approach to sleep disturbances in MDD, although with inconsistent results (Kupfer et al., 1992; Frieboes et al., 1997; Spier and de Lecea, 2000). However, despite these earlier findings, interest in this neuropeptide in MDD has declined over time, potentially due to the difficulties in unraveling the complexity of neuroendocrine changes in MDD.
Low SST has also been reported across cortical layers in schizophrenia (Morris et al., 2008) in the context of reduced parvalbumin (Lewis et al., 2001; Beasley et al., 2002; Hashimoto et al., 2003; Hashimoto et al., 2008; Sakai et al., 2008). In contrast, SST appears to be selectively downregulated in MDD, as parvalbumin and other GABA markers are unchanged in the dorsolateral prefrontal cortex of MDD subjects (Sibille et al., 2010). As suggested by the anatomical and functional diversity of GABA interneuron populations, changes in SST neurons, combined with other GABA- and disease-specific changes in related systems, may result in distinct pathophysiological outcomes. Hence, we speculate that the present findings reflect MDD-specific microcircuitry deficits, and that the consequences on associated information processing may vary across diseases, potentially underlying the prevalence of distinct symptom dimensions across diseases, i.e. working memory deficits in schizophrenia (Lewis and Gonzalez-Burgos, 2006) or altered mood regulation in MDD (Sibille et al., 2010). We believe that our replicated findings of low SST in brain areas that are relevant to a neural network implicated in the pathophysiology and treatment response in MDD (Seminowicz et al., 2004; Agid et al., 2007), provide a new perspective on SST as an inhibitory neuromodulatory peptide in the brain, in addition to its putative neuroendocrine-related dysfunction in MDD, and as a target for investigations with functional implication for local neuronal microcircuitry in MDD. Notably, the fact that SST was downregulated in dorsolateral prefrontal and cingulate cortices, despite variable functional changes in those areas (Seminowicz et al., 2004), suggesting low SST being a risk factor (of yet-unknown etiology), rather than a pathological consequence of the illness, as compensatory changes may show opposite patterns. SST is coexpressed and coreleased with GABA in interneurons in many parts of the human brain, including the sgACC. Thus low SST may provide a means to begin characterizing changes in the local microcircuitry that may be involved in the excitation/inhibition imbalance suggested in limbic brain areas in MDD (Maciag et al., 2010). Specifically, the SST+ neocortical circuitry inhibits distal dendrites on target neurons, compared to the soma-targeting parvalbumin+ inhibitory circuitry for instance.
Other than age and symptom number of the subjects, none of the clinical, demographic and technical parameters had any detectable effects on SST expression. This includes particulars of brain tissue collection postmortem (PMI, pH, RNA ratio, RIN), and clinical variables (race, remission status, antidepressants, mode of death). The fact that antidepressant exposure in rodent models results in either increase (Pallis et al., 2009) or no change (Surget et al., 2009) in SST mRNA levels, suggesting that the reduction in SST mRNA expression observed here is instead associated with the disease process of MDD. Furthermore, the absence of change of SST reduction in depressed subjects with antidepressant medication suggests that this mechanism is independent of treatment response or drug mechanism. The moderate inverse correlation between SST levels and symptom numbers suggest that low SST may contribute to disease severity, in addition to being associated with disease state. Thus, low SST may represent a stable vulnerability factor involved in the development of the illness and may determine in concert with other factors the severity of MDD. Accordingly, the more robust SST-related findings in female subjects would also be consistent with the increased vulnerability to develop episodes of MDD in that population.
In relation to age, SST levels progressively decline throughout adult life in control subjects (Glorioso et al., 2010), but were low at most ages in MDD subjects, displaying non-significant correlations with age. This was consistent across areas (Sibille et al., 2010) and cohorts (Fig.2). We previously discussed potential mechanisms and implications of consistently low SST in MDD subjects (Sibille et al., 2010). SST is expressed transiently (Viollet et al., 2008) and progressively decreases during development (Fung et al., 2010), hence by extension earlier in life, constitutive low levels of SST expression could result in alteration of normal brain development resulting in a greater vulnerability to depression throughout one's lifespan. At the other end of the lifespan, decreasing SST levels in normal subjects may reach critical threshold, below which the vulnerability to develop MDD increases; so age-dependent reduction in SST levels may represent a vulnerability factor underlying the increased risk for low mood symptoms in elderly subjects (Fiske et al., 2009). Finally, the reduced SST expression could be representative of an overall decrease in the structure and functional capacity of the SST+ subgroup of interneurons, and additional gene products and neurotransmitter present in these interneurons (e.g. neuropetide Y, GABA) may participate in mediating the cellular dysfunctions leading to altered brain function and depressive states.
In summary, we have established a robust reduction in SST mRNA and precursor peptide in MDD subjects, with age, symptom number, and sex modulating that deficit. Alterations in SST-bearing GABA neurons and/or in SST signaling may thus represent a pathophysiological entity that contributes to sgACC dysfunction in both male and female subjects with MDD.
Supported by the following grants from the National Institute of Mental Health (NIMH): MH084060 (ES), MH077159 (ES) MH45156 (DAL), and MH084053 (DAL). The funding agency had no role in the study design, data collection and analysis, decision to publish and preparation of the manuscript. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Mental Health or the National Institutes of Health.
Statement of Interest. David A. Lewis currently receives investigator-initiated research support from the BMS Foundation, Bristol-Myers Squibb, Curridium Ltd and Pfizer and in 2008-2010 served as a consultant in the areas of target identification and validation and new compound development to AstraZeneca, BioLine RX, Bristol-Myers Squibb, Hoffman-Roche, Lilly, Merck, Neurogen and SK Life Science. The other authors have no interests to declare.
Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
PubMed Central Canada is a service of the Canadian Institutes of Health Research (CIHR) working in partnership with the National Research Council's Canada Institute for Scientific and Technical Information in cooperation with the National Center for Biotechnology Information at the U.S. National Library of Medicine(NCBI/NLM). It includes content provided to the PubMed Central International archive by participating publishers.


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Graffit Gallery Hotel - Varna
- Free WiFi and free parking
Your hotel has its own restaurant serving breakfast, lunch, dinner and brunch where you'll find a selection of items to try. Go for a dip in the indoor pool during your stay. There is also a bar/lounge where guests can enjoy drinks.
A fitness center, a sauna, massage/treatment rooms and spa services are among the leisure facilities on offer. Guests can make use of the free WiFi and high-speed (wired) Internet access.
Main amenities
- 55 guestrooms
- Restaurant and bar/lounge
- Indoor pool
- Nightclub
- Breakfast available
- Fitness center
- Spa services
- Business center
- Airport shuttle
- 24-hour front desk
- Air conditioning
- Daily housekeeping
What's around
- Heart of Varna
- Varna Archaelogical Museum (0.4 mi / 0.7 km)
- Varna Aquarium (0.6 mi / 0.9 km)
- Sea Garden (0.7 mi / 1.1 km)
- Dormition of the Theotokos Cathedral (0.8 mi / 1.2 km)
- Ticha Stadium (1.9 mi / 3.1 km)
Nice hotel. Food from the restaurant was amazing. Glad I stayed here.
Enter dates to check prices
Hotel Info: 1-877-214-4288from $71
- Junior Suite, 1 King Bed with Sofabed
- Suite, 1 King Bed with Sofabed
- Standard Room, 1 King Bed
- Deluxe Room
- Superior Room
Also popular with travelers from the USA
At a glance
Key facts
Hotel size
- This hotel has 55 rooms
- This hotel is arranged over 4 floors
- Check-in time 2 PM-Midnight
- Check-out time is noon
- Express check-in/out
Required at check in
- Credit card or cash deposit required
- Government-issued photo ID required
Travelling with others
- No pets or service animals allowed
- Free WiFi and wired Internet access in public areas
- Free WiFi and wired Internet access in rooms
- Airport shuttle (available on request) *
- Free valet parking
Other information
- Resort fee included
In the hotel
- Breakfast (surcharge)
- Restaurant
- Bar/lounge
- Coffee shop/café
- 24-hour room service
- Indoor pool heated
- Fitness facilities
- Spa services on site
- Spa treatment room(s)
- Nightclub
- Sauna
- Business center
- Number of meeting rooms - 4
- Conference space
- Meeting rooms 4
- 24-hour front desk
- Concierge services
- Tours/ticket assistance
- Limo or Town Car service available
- Dry cleaning/laundry service
- Laundry facilities
- Free newspapers in lobby
- Luggage storage
- Number of buildings/towers - 1
- Year Built 2011
- Elevator/lift
- ATM/banking
- Accessible bathroom
- In-room accessibility
In the room
- Climate control
- Air conditioning
- Minibar
- Coffee/tea maker
- Bathrobes
- Slippers
- Iron/ironing board (on request)
- Pillow menu
- Blackout drapes/curtains
- Soundproofed rooms
- Turndown service
- Egyptian-cotton sheets
- Individually decorated
- Individually furnished
- Private bathroom
- Deep soaking bathtub
- Bidet
- Hair dryer
- 32-inch LCD TV
- Satellite TV channels
- Desk
- Free WiFi
- Daily housekeeping
- In-room safe (laptop compatible)
Special features
DiningRed Canape - This restaurant serves breakfast, brunch, lunch, and dinner. Reservations are required.
Awards and affiliations
- The property is a member of the Leading Hotels of the World.
Graffit Gallery Hotel - Varna's small print
Only registered guests are allowed in the guestrooms.
Children under 13 years old are not allowed in the swimming pool or fitness facility without adult supervision.
For transfers, guests must contact the property before arrival at the number on the booking confirmation.
Mandatory fees
The charges below are included in the total price displayed:
- Resort fee
Optional extras
Late check-out can be arranged for an extra charge of BGN 80
Breakfast is offered for an extra charge of BGN 18 per person (approximately)
Airport shuttle service is offered for an extra charge of BGN 25 per person (roundtrip)
We have included all charges provided to us by this hotel. However, charges can vary, for example, based on length of stay or the room you book.


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A Whole Book Full of Incredible Never-Before-Seen Star Trek Costume Pictures
We're pretty obsessed with the costumes from Star Trek, both the original series and the later iterations. After all, Trek has a long and proud record of pushing the fashion envelope, from its military pajamas to its alien lingerie. Here's a look inside a stunning new book about Star Trek's greatest costumes. »


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There is so much to say about the Dolomites. As you approach Italy, an imposing mountain range surrounds many chateaus and old villages. In the older and less touristy areas of the Dolomites, there is an immediate feeling of being in the early 1800's. 515 more words
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Just Keep Swimming
Well, I'm two weeks into my 6-week summer semester and I am overwhelmed to say the least. I've been learning Mandarin, Chinese culture and history, and preparing to obtain my TESOL certification. 248 more words
#27 Hartford, Connecticut
Really happy to have finally made it to Connecticut and that I was able to cross off another state from my list. In not having much money, I decided to make it a day trip (no hotel room needed). 906 more words
It can sometimes be hard to step outside the everyday tasks that our library staff are accountable for, such as helping our residents with their questions; ensuring our buildings are safe for the public; and providing programs and classes that meet the needs of our community, but through the efforts of our amazing staff we also manage to apply for and manage grants, submit proposals for speaking engagements at local and national conferences, and work with other local organizations in collaborative efforts. 186 more words
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Had a great time last night at the Lindsey Stirling concert! It was incredible. I don't think I have ever been to a concert like this one. 211 more words
Financial and homeownership team thanks state Sen. Booher
One of the things that we have been talking about over the past few months is the importance of developing our strategic communications to work on relationship-building. 274 more words
Helping build little libraries for western Wisconsin
Gathering at Hudson Senior High School, almost 20 Luther Auto team members from the Chevrolet and Chrysler stores helped assemble 41 Little Free Library kits, enough to supply all the St. 43 more words


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Get ready for an awesome introduction to Drupal for nonprofits and social change makers! We'll cover the power of Drupal to create a web presence and online community for your cause, a walk-through for beginners, and explore some exciting sites built on the Drupal platform. Presenters: Boris Mann,
BootupLabs Scott Nelson, Karianne Blank -
FearlessCity.ca Phillip Djwa,
Agentic Event Starts @ 5:30! This is a FREE Event Sponsored by the wonderful folks @
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WorkSpace! This event is also listed on Facebook! --
I was expecting a slightly more technical examination of Drupal. While it was nice to see what a similar non-profit has done with Drupal, I would've liked more nuts-and-bolts information instead of high level discussions.
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New Hampshire Film Festival takes place October 15-18 in Portsmouth. More...
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Next New Hampshire High School Short Film Fest On Tour screening 9/16 at O'neil Cinemas in Epping. More...
No sales or income tax. Diverse locations in close proximity. Our creative atmosphere. Learn more about why New Hampshire is perfect for independent filmmakers!
From camera crew to production assistants and everything in between--browse our directory of industry professionals and support services and hire locally!
From the New Hampshire Film Festival in Portsmouth to the statewide High School Short Film Festival, there's something for everyone!
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Nigel Milsom's portrait of his friend, the Sydney barrister Charles Waterstreet - who defended the artist in court - has won the Archibald Prize. It's not the most sympathetic portrait ever painted with at least one critic describing the dark almost monochromatic work as 'vampiric'.
A mover and shaker in the Australian art world, Lisa Slade is the director of public programs at the Art Gallery of South Australia. She's is the driving force behind the 2016 Adelaide Biennial and she is also working on a project exploring a little known artform: objects made by Australian soldiers in the trenches during wartime.
Sculptor, installation, and performance artist Kon Dimopoulos shares the artworks on his top shelf.
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New Australian play All My Love brings their little known but surprisingly passionate love affair between Henry Lawson and the poet Mary Gilmore to the stage.
Stephen Sparks uses his blog Writers No One Reads to raise awareness of the 'forgotten, neglected, abandoned, forsaken, unrecognized, unacknowledged, overshadowed, out-of-fashion, and under-translated'.
German painter Elise Blumann found inspiration in the landscapes of Western Australia, after fleeing Nazi Germany.
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George Williams reviews Sabaa Tahir's An Ember in the Ashes, and Cixin Liu's The Three-Body Problem.
Described as one of the most of most satisfyingly Australian novels in years, The Mothers by Rod Jones interweaves the stories of three generations of Australian women living through extraordinary times.
Âu Cô is Vietnamese — Midori is Japanese. In Hoa Pham's novel Wave, the two young women are international students in Melbourne, where they navigate freedom, obligation, and alienation.
A nine-meter shiny stainless steel gnome now graces the peninsula Link Freeway south of Melbourne
This novel walks through the streets and onto the stage in 1920s Sydney with a lyre bird, a woman in trousers and the ghosts of both Houdini and the First World War.
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The Antarctic Pavilion at the 2015 Venice Biennale asks what role art is to play in the political and social life of Antarctica.
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Milliner Richard Nylon has curated a flamboyant 'House of Ideas' at Fairhall, the home of collector William Johnston in East Melbourne.
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A town on the brink of breaking into the big leagues, Reno is having a moment. And one could argue that summer is one of the best times to check out the growing outdoor and culinary scene, thanks to a handful of festivals that showcase Reno at its best. From a town-wide art festival to a hot air balloon festival that covers the sky with inflatable art, here are our favorites.
Emerging as a city with a distinct culture of its own — thanks to an economic turnaround attributed in part to Tesla's move to the area — Reno has come alive in recent years as an affordable playground for foodies and outdoor adventurers. There are now more ways than ever to get there, too, with a new direct flight on JetBlue from New York's JFK, and the city earned a spot on our Top Budget Destinations of 2015 list. Even better, the thousands of hotel rooms throughout the area average less than $100 per night, offering remarkable value. Here, a deeper look at what's on offer, with four more great reasons you should visit Reno now.
After a relationship has tanked to the point of no return, there's nothing quite like getting in the car — either by yourself or with a bestie or two — and taking your mind off everything on the open road. So queue up Tom Petty's "Free Falling" and set the GPS for one of these epic post-breakup road trips.
Reno has undergone a serious transformation in recent years, most notably with the much-celebrated arrival of Tesla, ushering in 22,000 jobs and an estimated economic impact upwards of $100 billion over the next 20 years. We hopped aboard the inaugural JetBlue flight direct from JFK to Reno to see the emerging city for ourselves. While there, we had the chance to discover The Atlantis Casino Resort Spa. When it comes to the best in budget-friendly accomodations that don't compromise luxury, we think the property ranks high for it's proximity to the airport, newly renovated spa, and ample gaming floor. Here's our full report.
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a laymans thoughts . are they not simple selling 140 mil shares @ 1.25 , why so cheap ?
well over doubling the outstanding # of shares


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Tofino - Brand New 5 Star Executive Rental
From $152 / night
11 travelers
viewed this property in the past week
Description from the owner
Description from the owner
Bedrooms: 2/
Bathrooms: 2/
Sleeps: 4/
Type: Apt. / Condo
We are an executive rental. You wake up to the sun rising over the ocean from your 5 star hotel bed with 800 thread count sheets in your lofted bedroom with 19' glass windows. You have your coffee in our gourmet kitchen outfitted with everything you need to make your special meal using the organic ingredients and fresh seafood available just outside your door...you decide to eat out instead choosing from a multiple of possibilities including the Relais + Chateaux acclaimed Wickaninnish Inn (you'd stay there but you prefer over 1200 sq ft of private living space and a 270 sq ft deck). We are located in downtown Tofino on Main Street and you can ...Read more
About the owner
About the owner
Madelaine Kelly
Madelaine Kelly
- Response rate: 90%
- Response time: Within a day
- Calendar updated: yesterday
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Additional Location Information
Downtown Tofino
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Beach or lakeside relaxation, City vacations, Waterfront
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|Publication number
|Publication type
|Publication date
|Oct 2, 1973
|Filing date
|Dec 30, 1971
|Priority date
|Jul 30, 1971
|Also published as
|Publication number
|Shilling M
|Original Assignee
|Rca Corp
|Export Citation
|BiBTeX, EndNote, RefMan
|Patent Citations (3), Non-Patent Citations (1), Referenced by (24), Classifications (12)
|External Links: USPTO, USPTO Assignment, Espacenet
nited States Patent 11 1 Shilling [H1 3,763,396 1 Oct. 2, 19 73 INTERFERENCE SUPPRESSION CIRCUITS [75] Inventor: Michael John Shilling, Kingston,
England [73] Assignee: RCA Corporation, New York, NY.
[22] Filed: Dec. 30, 1971 [21] Appl. No.: 214,120
[30] Foreign Application Priority Data July 30, 1971 Great Britain 36,058/7l [52] US. Cl. 315/307, 307/252 B, 307/305 [51] Int. Cl. G05f 1/20, 1105!) 37/02, 05b 39/08 [58] Field of Search 315/30731 1;
[56] References Cited UNITED STATES PATENTS 3,447,067 5/l969 Spofford 307/305 X 8/1969 Morgan 307/252 B 3/l970 Babcock... 307/305 X OTHER PUBLICATIONS Galloway, Using the Triac for Control of AC Power pp. 1,9,10,11, G.E. Application Notes 200.35, 3/1966.
Primary Examiner-Alfred L. Brody AttorneyEdward J. Norton 57 ABSTRACT 1 In a thyristor switching circuit including an LC filter, means responsive to the conduction state of the thyristor are provided for preventing the thyristor from commutating into an off state during midcycle.
10 Claims, 11 Drawing Figures Patented Oct. 2,1973
2 Sheets-Sheet 1 TIgIAC CONTROL CKT.
PRIOR ART MG l G 2 L ,A) N N I I IT MI. MI R 2 R ET E T T N W A A M M PRIOR ART CONTROL CKT.
T R A R l R P TRBIAC CONTROL CKT Patented Oct. 2, 1973 3,763,396
2 Sheets-Sheet 2 llNTERlFERENCE SUPPRESSION CIRCUITS This invention relates to thyristor switching circuits and, more particularly, to interference suppression circuits for use therewith in controlling the supply of power to a load.
The triac or bidirectional triode thyristor is a three terminal solid-state switch which is normally triggered into conduction by the application of a pulse to its gate electrode in the presence of an applied bias to its main terminal electrodes, the direction of current conduction through the device being dependent upon the polarity of the applied bias.
The popularity of triac controlled incandescent lamp dimmers has resulted in the commercialization of a multiplicity of such circuits, some satisfactory and others suffering from defects which often make them unacceptable in a domestic environment. These circuits are generally of the phase control" type wherein the power delivered to the load is controlled by variation of the phase angle at which triac switching initiates current flow. Basically they include, in addition to the triac, an adjustable RC time constant circuit for controlling the phase angle at which the triac is switched into its conducting or on" state, a triggering element such as a diac for providing a pulse to the gate electrode of the triac when the time constant circuit has been charged to the desired level, and a filtering network to provide radio frequency interference (RFI) suppression.
One of the problems encountered in the use of triac dimmer circuits is a phenomenon known as flicker which, as its name implies, produces an objectionable visual flickering in the lamp load. This effect is generally more apparent in the case of lighting loads of less than 1100 watts. As will be explained in more detail hereinafter, the severity of the problem is related to the RFI suppression requirements imposed upon the circuit and the operating environment. For example, in the United States simplified RFI suppression filters consisting of a 0.1 microfarad (pf) capacitor and a 0.1 millihenry (mh) inductor are generally used with satisfactory results, due to the absence of commercial broadcasts in the ISOKHz-ZSOKHz band. In countries which utilize this band for broadcast purposes the use of such filters are precluded. In Great Britain, for example, a regulatory provision has been proposed which would impose stringent RFI suppression requirements, thereby further compounding the flicker problem.
A switching circuit in accordance with the present invention comprises a thyristor adapted to control the supply of power to a load; a time constant circuit for controlling the phase angle at which said thyristor is switched into conduction; an LC filter; and means responsive to the conduction state of said thyristor for preventing said thyristor from commutating into an off state during midcycle.
The present invention will be more readily understood upon reading the present specification in conjunction with the accompanying drawing wherein:
FIG. 1 is a schematic diagram of a traic as used in this application;
FIGS. 2-4 are generalized representations of dimmer circuits, including radio frequency interference (RFI) networks, in accordance with the prior art;
FIG. 5 is a circuit diagram of a triac dimmer circuit which embodies the present invention; and
FIGS. 60, 6b and 6c and 7a, 7b and 7c are a series of waveforms helpful in understanding the present invention.
To understand the theories which have been advanced to explain the cause of the flicker phenomenon, it is desirable to first discuss some of the characteristics of a triac which contribute to the problem; for example, the critical rate of rise of off-state voltage, holding current, and tum-off time characteristics. Also significant is an understanding of the RFI problems associated with triac switching circuits, how they have been overcome in the prior art, and how they contribute to the flicker problem.
Referring first to FIG. 1, it will be seen that a triac is a three terminal solid-state switch having a first main terminal electrode designated T,, a second main terminal electrode designated T and a gate electrode designated G. The triac is bidirectional, dependent upon the polarity of potential applied across its main terminal electrodes, and can be triggered into conduction in any of four operating modes as summarizedbelow (all polarities taken with terminal T as the point of reference potential):
Operating Quadrant V V I positive positive I negative positive III positive negative III negative negative The gate-trigger requirements of the triac are different in each of the operating quadrants, generally being most sensitive in the I and III modes. When triggered into conduction, the potential drop across the device is negligible and all of the electrodes (i.e., T T and G) operate at substantially the same potential. When the device is in a nonconducting or off state, terminal T and gate electrode G will be at substantially the same potential and terminal T will be at a substantially different potential dependent upon the applied source of potential. This is due to the fact that the gate electrode G and main terminal electrode T are effectively coupled via a low internal impedance.
Because of its internal capacitance, the forward blocking capability of a triac is sensitive to the rate at which the forward or bias voltage is applied across the main terminals of the device. A steep rising voltage impressed across the main terminals causes a capacitive charging current which is a function of the rate ofrise of the off-state voltage (i= C dv/dt) to flow through the device; off-state voltage being defined as that range of voltage, either transient or steady state, which the device can withstand without switching into conduction. If the rate of rise of forward voltage exceeds a critical value, the capacitive charging currentmay become large enough to trigger the device. The steeper the wavefront of applied forward voltage, the smaller the value of breakover voltage, i.e., the voltage at which the device will switch into conduction. This dv/dt capability (i.e., the ability to withstand a charging current without triggering) is temperature sensitive, decreasing as the temperature rises.
, After a triac has been switched into its conducting or low impedance state, a certain minimum holding current is required to maintain the device in such an on state. Should the current through the device drop below this critical level of holding current the triac cannot maintain regeneration and will revert to its high impedance or off" state. This holding current parameter is also temperature sensitive, increasing as the temperature decreases.
Turn-off time is defined as the time interval between zero current and the time of reapplication of positive forward blocking voltage under specified conditions with the device remaining in the off state after having been in the on state.
The fast switching action of triacs when they turn on into resistive loads (e.g., light bulbs) causes the current to rise to the instantaneous value determined by the load in a very short period of time. Triacs switch from the high to the low impedance state within 1 or 2 microseconds and the current through the device must rise from essentially zero to full-load value during this period. This fast switching action produces a current step which is largely composed of high-harmonic frequencies of several megahertz that have an amplitude varying inversely as the frequency. In phase-control applications, such as light dimming, this current step is produced on each half-cycle of the input voltage. Because the switching occurs many times a second (e.g., I times a second for a 50 cycle frequency), a noise pulse is generated into frequency sensitive devices such as AM and shortwave radios causing annoying interference. The amplitude of the high frequency components of the current step is generally of such low level as not to interfere with TV or FM radio reception. Although the level of radio frequency interference (RFI) produced by triac switching is well below that produced by most ac/dc brush type electronic motors, some type of RFI suppression network is usually added.
There are two basic types of radio frequency interference associated with the switching action of triacs. One form, i.e., radiated RFI, consists of the high frequency energy radiated through the air from equipment. In most cases, this radiated RFI is insufficient to cause any significant interference unless the radio is located very close to the source of radiation.
Of more significance is conducted RFI which is carried through the power lines and affects equipment connected to the same power lines. Because the composition of the current waveshape consists of higher frequencies, a simple choke placed in series with the load increases the current rise time and reduces the amplitude of the higher harmonics. To be effective, however, such a choke must be quite large. More efi'ective filters, and ones that have been found adequate for most light dimming applications, are shown in FIGS. 2 and 3. The LC filters shown in FIGS. 2 and 3 provide adequate attenuation of the high-frequency harmonics and reduce the noise interference to a low level. The capacitors, which are connected across the entire network, bypass high frequency signals so that they are not coupled to any external circuits through the power lines. I
As previously discussed, an objectionable visual flickering is often encountered in the use of triac dimmer circuits with lighting loads of less than l00 watts.
Although the exact cause of this problem has not been resolved, some theories have been advanced in the literature.
The problem is recognized by J. H. Galloway in a March, 1966 Application Note published by the General Electric Company entitled Using the Triac for Control of AC Power. In accordance with the theory advanced therein, and with reference to the circuits shown in FIGS. 2 and 3 of this specification, the RFI suppression filter (210, 310) and the triac of the respective circuits form a resonant discharge circuit having a resonant frequency governed primarily by the parameters of the RFI filter which in turn are determined by the desired degree of RFI suppression; the discharge circuit being dependent upon the impedance of the load (220, 320) for damping, the condition being worse for small lighting loads (i.e., incandescent lamps of less than watts) which contribute little damping to the circuit. If the Q of the resonant circuit increases beyond a critical level, the oscillatory current generated by the switching transient in the resonant circuit will be of sufficient amplitude and polarity to cause the triac to turn off. To obtain proper operation with low wattage loads, it is suggested that additional damping be built into the RFI suppression filter. This can be done by adding a resistor R and an additional capacitor C as shown in FIG. 4.
An additional discussion of the flicker problem appears in RCA Application Note 4316 published July, 1970 by A. E. I-Iilling and entitled Triac Control Circuit for Incandescent Lamps." Hilling also recognizes that at the resonant frequency of the suppression components the oscillatory current is magnified by the loaded Q of the circuit and, if the amplitude of this current is sufficiently large to override the main load current, it will cause the triac to switch off. Accordingly, in addition to recognizing the solution set forth by Galloway, Hilling recognizes that by reducing the loaded 0 of the RFI network the amplitude of the oscillatory current may be reduced such that it cannot overcome the load current. This can be achieved by using the circuit of FIG. 4 or by using the circuits shown in FIGS. 2 and 3 with lossy chokes (i.e., chokes having an unloaded Q approximately equal to unity) in lieu of the high Q (e.g., ferrite) chokes commonly used.
Both I-Iilling and Galloway recognize that triacs with slow dv/dt capability or poor turn-off characteristics may not suffer from the flicker effect because they are incapable of responding quickly enough and consequently remain in the conducting state.
Although both of the solutions proposed by the forementioned articles overcome the flicker problem, the introduction of an additional RC circuit of the size required for the circuit of FIG. 4, or the use of lossy chokes in lieu of high Q chokes, is expensive. Moreover, since a lamp dimming circuit is generally designed to fit into a very confined wall space, it is desirable not to introduce additional components which will contribute any significant additional bulk to the circuit.
FIG. 5 is illustrative of a light dimming circuit in accordance with the present invention. Those skilled in the art will recognize the circuit of FIG. 5 as a basic double time-constant light dimmer circuit including a triggering diac 514 and an RFI suppression filter 510, with the addition of an RC circuit 530 connected between the gate electrode G and terminal electrode T of triac 540.
Tuming-now to a description of the operation of the circuit shown in FIG. 5, during the beginning of each half cycle the tn'ac 540 is in the off state and the entire line voltage 550 appears across the main terminals of the triac 540. At the same time capacitors 560 and 570 are charged through the potentiometer comprising resistors 575, 576, 577 and 578. When the voltage across capacitor 570 reaches the breakover voltage of the diac 514, capacitor 570 discharges through diac 514 into the gate electrode G of the triac 540 thereby causing the triac 540 to trigger into conduction. At this point in time the line voltage 550. is transferred from the triac 540 to the load 580 for the remainder of the half cycle. If the potentiometer resistance is reduced via variable resistor 577, capacitor 570 will charge more rapidly and diac 514 will breakover earlier in the cycle, increasing the power supplied to the load 580 and hence the intensity of the light. If the potentiometer resistance is increased, triggering occurs later in the cycle, load power is decreased, and the light intensity reduced. Capacitor 560 reduces hysteresis in the circuit by charging to a higher voltage than capacitor 570 and restoring some charge to capacitor 570 after triggering.
In the circuit shown in FIG. 5, should the triac 540 begin to commutate into the off state during midcycle (e.g., in response to the oscillatory current of the resonant discharge circuit as discussed supra), the potential at terminal T of the triac 540 with respect to the gate electrode G will attempt to instantaneously rise (as lim-' ited by the stray capacitance of the triac) to the levelof the supply voltage 550. The resulting change in potential difference across terminal T and gate electrode G causes a charging current (i C dv/dt) to flow through the RC circuit 530 comprising resistor 532 and capacitor 531 which current is in turn fed to the gate electrode G and maintains the triac 540 in its conducting state. Capacitor 531 is selsected such that it is incapable of triggering the triac 540 from the line voltage 550 when the triac is in the off state. It will be appreciated, however, that due to the substantially instantaneous rate of rise of voltage at terminal T, of the triac should it attempt to commutate off during midcycle, a relatively small capacitor will provide a relatively large charging current. Resistor 532 is selected to limit the current provided by capacitor 531 to triac 540 at turn on and also serves to help prevent the triac from inadvertently triggering into conduction due to small transients on'the power line.
The waveforms of FIGS. 6 and 7 are illustrative of triac voltage (V triac current (I and gate current (I for the circuit of FIG. 5 supplying a watt lamp from a 240 volt 50 cycle source, with the RC circuit 530 omitted (i.e., in accordance with the prior art) and present, respectively. In FIG. 6, which is representative of the circuit undergoing flicker, it will be seen that the triac rapidly switches into and out of conduction several times during the course of each half cycle. In FIG. 7, which is representative of a circuit in accordance with the present invention (i.e., FIG. 5), it will be seen that the triac is prevented from switching off during midcycle by the spike of gate current (I provided by RC circuit 530, as described supra.
The embodiment depicted in FIG. 5 was constructed using the following components, and the waveforms of FIG. 6 and 7 are based thereon:
Element No. Value 512 L2 millihenry 513 0.022 microfarads 514 RCA 40583 diac 540 RCA 40669 triac 560, 570 0.] microflrads 575 5600 ohms 576 250,000 ohms 577 500,000 ohms 578 3900 ohms 5M 2200 picofarads 532 47 ohms Accordingly, there has been disclosed an inexpensive means for eliminating the objectionable visual flickering often encountered when using triac dimmer circuits with small lighting loads.
What is claimed is:
1. In a switching circuit comprising a thyristor adapted for connection to an alternating current source and a load to be supplied from said alternating current source; means for connecting said thyristor in circuit with said load and said alternating current source; a time constant network responsive to said alternating current source and connected in circuit with said thyristor for controlling the phase angle at which said thyristor is switched into conduction; and a filtering net- .work connected in circuit with said thyristor for the suppression of interference generated by the switching action of said thyristor, the improvement comprising:
circuit means coupled to said thyristor and responsive to the conduction state of said thyristor for preventing said thyristor from commutating into an off state during midcycle.
2. The invention as defined in claim 1 wherein said filtering network comprises an inductor-capacitor circuit which forms a resonant discharge circuit with said thyristor that is dependent upon the impedance of said load for damping, and wherein the Q of said resonant circuit is above a critical level such that the oscillatory current of said resonant discharge circuit would be sufficient to cause said thyristor to commutate into an off state during midcycle.
3. The invention as defined in claim 1 wherein said thyristor comprises a triac having first and second main terminal electrodes and a gate electrode, and wherein said circuit means comprises a further time constant network connected between a given one of said main terminal electrodes and said gate electrode.
4. The invention as defined in claim 3 wherein said further time constant network comprises a resistorcapacitor circuit.
5. A switching circuit for controlling the supply of power to a load from a source of alternating current comprising:
a triac having first and second main terminal electrodes and a gate electrode;
means for connecting said first and second main terminal electrodes in circuit with said alternating current source and said load;
a time constant network responsive to said alternating current source and connected in circuit with said triac electrodes for controlling the phase angle at which said triac is switched into conduction;
an interference suppression network connected in circuit with 'said main terminal electrodes of said triac, said suppression network and said triac forming a resonant discharge circuit which is dependent upon the impedance of said load for damping, the Q of said resonant circuit being above a critical level such that the oscillatory current of said resonant discharge circuit would be sufficient to cause said triac to commutate into an off state during midcycle; and A circuit means connected between a given one of said main terminal electrodes and said gate electrode, said circuit means operating to provide current to said gate electrode in response to a rate of change of voltage of greater than a critical value across said given terminal electrode and said gate electrode to prevent said triac from commutating off during midcycle.
6. A switching circuit as defined in claim wherein said circuit means comprises a series resistor-capacitor network.
7. In a switching circuit comprising a triac having first and second main terminal electrodes and a gate electrode; means for connecting said main terminal electrodes in circuit with an incandescent lamp load and an alternating current source; a time constant network responsive to said alternating current source and connected in circuit with said triac electrodes for controlling the phase angle at which said triac is switched into conduction; and a radio frequency interference suppression network comprising an inductor and a capacitor connected in circuit with said main terminal electrodes, wherein said suppression network and said triac form a resonant discharge circuit which is dependent upon the impedance of said incandescent lamp load for damping, and wherein the Q of said resonant circuit is above a critical level such that the oscillatory current of said resonant discharge circuit would be sufficient to cause said triac to commutate into an off state during midcycle thereby causing said lamp load to flicker, the improvement comprising:
a resistor-capacitor network connected between a given one of said main terminal electrodes and said gate electrode, said network operating in response to a rate of rise of greater than a given value of the voltage across said gate electrode and said given terminal electrode to provide current to said gate electrode to prevent said triac from commutating into an off state during midcycle, whereby said lamp load is prevented from flickering.
8. In a circuit which includes a thyristor having main electrodes and a gate electrode, a load in circuit with said thyristor, connections for a source of power coupled to said load and thyristor, and reactive elements -in circuit with the thyristor and load forming a resonant circuit therewith, and which circuit tends to be driven into oscillation at a frequency substantially higher than the power frequency when said thyristor is turned on by a turn-on signal applied to said gate electrode, said oscillations being at an amplitude sufficient intermittently to turn off said thyristor, a circuit for lessening said tendency of said thyristor intermittently to turn off comprising:
a feedback path which exhibits a relatively low impedance at the frequency of said oscillations and a relatively high impedance at the power frequency, connected between a main electrode of said thyristor at which said oscillations appear and said gate electrode, for feeding back to said gate electrode a signal which tends to maintain said thyristor in its conducting state when an oscillation across said main electrodes tends to drive said thyristor to cut off.
9. In a circuit as set forth in claim 8, said feedback circuit comprising a resistor of relatively low value in series with a capacitor.
10. In a circuit as set forth in claim 8, the means for turning on said thyristor comprising a phase delay network coupled to said connections and a triggering device connected between said phase delay network and said gate electrode, said feedback path being connected from said main electrode to a circuit point between said triggering device and said gate electrode.
|Cited Patent
|Filing date
|Publication date
|Feb 27, 1967
|May 27, 1969
|Gen Electric
|Hysteresis free phase control circuit using silicon bilateral switch
|Oct 24, 1965
|Aug 12, 1969
|Gen Electric
|Commutation scheme for power semiconductor circuits for limiting rate of reapplied voltage and current
|Jun 19, 1967
|Mar 10, 1970
|Gen Electric
|Discharge lamp control circuit with semiconductor actuating means therefor
|Galloway, Using the Triac for Control of AC Power pp. 1,9,10,11, G.E. Application Notes 200.35, 3/1966.
|Citing Patent
|Filing date
|Publication date
|Apr 26, 1974
|Aug 5, 1975
|Rca Corp
|Circuit for supplying power to a load
|Dec 11, 1978
|Jun 3, 1980
|Candel, Inc.
|Remote thermostat heater and method of control therefor
|Feb 14, 1980
|Mar 23, 1982
|Honeywell Inc.
|Positive differential alternating current switching means
|Apr 29, 1985
|Jun 30, 1987
|Starter Systems, Inc.
|Combined ignitor and transient suppressor for gaseous discharge lighting equipment
|Mar 31, 1986
|Mar 1, 1988
|U.S. Philips Corporation
|Adaption circuit for operating a high-pressure discharge lamp
|Oct 27, 1993
|Mar 19, 1996
|Lighting Control, Inc.
|Switchmode AC power controller
|Mar 8, 1993
|Apr 2, 1996
|Beacon Light Products, Inc.
|Lamp bulb having integrated lighting function control circuitry and method of manufacture
|Jul 30, 1996
|May 25, 1999
|Molex Incorporated
|Trickle power supply
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|Feb 20, 2007
|Henry Michael Gannon
|Triac-based, low voltage AC dimmer
|May 28, 2010
|Sep 3, 2013
|Huadao Huang
|Feather-touch dimming switch
|Nov 23, 2010
|Mar 4, 2014
|Lutron Electronics Co., Inc.
|Two-wire dimmer switch for low-power loads
|May 15, 2013
|Mar 4, 2014
|Lutron Electronics Co., Inc.
|Two-wire dimmer switch for low-power loads
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|Lutron Electronics Co., Inc.
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|Lutron Electronics Co., Inc.
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|Lutron Electronics Co., Inc.
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|Feb 17, 2015
|Lutron Electronics Co., Inc.
|Load control device for high-efficiency loads
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|Lutron Electronics Co., Ltd.
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|U.S. Classification
|315/307, 327/582, 315/208, 315/199, 327/455
|International Classification
|Cooperative Classification
|European Classification


text:
Healthcare Equipment and Supplies
Company Overview of AOI Medical, Inc.
Executive Profile
Fred A. Achecar Jr., M.D.
Non Executive Director, Member of Nominations & Governance Committee and Member of Audit Committee, AOI Medical, Inc.
|Total Calculated Compensation
|This person is connected to 1 Board Members in 1 different organizations across 1 different industries.
See Board Relationships
Fred A. Achecar, Jr., M.D. is a Partner at Resurgent Orthopaedics of Atlanta. Dr. Achecar serves as Chief of Orthopaedic Surgery of WellStar Douglas Hospital, Georgia. Dr. Achecar has been Non Executive Director of AOI Medical Inc. since May 23, 2006. Dr. Achecar was accepted to the Campbell Clinic in Memphis, Tennessee where he completed his residency. Dr. Achecar earned his B.S. from the University of Notre Dame, and his M.D. from Tulane University School of Medicine. ...
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